Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3.
Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3.
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DOI：
10.1083/jcb.149.6.1309
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发表时间：
2000-06-12
期刊：
影响因子：
--
通讯作者：
Weiss SJ
中科院分区：
文献类型：
--
作者：
Hotary K;Allen E;Punturieri A;Yana I;Weiss SJ
在组织侵入事件中，迁移细胞通过动员未定义的蛋白水解酶穿透富含I型胶原的间质组织。为了筛选介导胶原侵袭活性的基质金属蛋白酶（MMP）家族的成员，开发了体外模型系统，其中MDCK细胞被稳定转染以过表达与基质重塑状态相关的十种不同MMP中的每一种。然后用分散因子/肝细胞生长因子（SF/HGF）刺激MDCK细胞，以在I型胶原或间质基质上启动侵袭和小管形成，以确定MMPs加速、修改或破坏形态发生反应的能力。分泌型胶原酶（MMP-1和MMP-13）、明胶酶（明胶酶A或B）、基质溶解素（MMP-3和MMP-11）或基质溶解素（MMP-7）均不影响SF/HGF诱导的反应。相比之下，膜锚定金属蛋白酶，膜1型MMP，膜2型MMP和膜3型MMP（MT 1-，MT 2-和MT3-MMP）各自修改形态发生程序。在测试的三种MT-MMP中，只有MT 1-MMP和MT 2-MMP能够直接赋予侵袭能力差的细胞穿透I型胶原基质的能力。MT-MMP依赖性侵袭独立于proMMP-2活化进行，但需要酶被膜锚定到细胞表面。这些发现表明，MT-MMP表达细胞可以渗透和重塑I型胶原丰富的组织，通过使用膜锚定的金属蛋白酶作为细胞周围的胶原酶。
During tissue-invasive events, migrating cells penetrate type I collagen-rich interstitial tissues by mobilizing undefined proteolytic enzymes. To screen for members of the matrix metalloproteinase (MMP) family that mediate collagen-invasive activity, an in vitro model system was developed wherein MDCK cells were stably transfected to overexpress each of ten different MMPs that have been linked to matrix remodeling states. MDCK cells were then stimulated with scatter factor/hepatocyte growth factor (SF/HGF) to initiate invasion and tubulogenesis atop either type I collagen or interstitial stroma to determine the ability of MMPs to accelerate, modify, or disrupt morphogenic responses. Neither secreted collagenases (MMP-1 and MMP-13), gelatinases (gelatinase A or B), stromelysins (MMP-3 and MMP-11), or matrilysin (MMP-7) affected SF/HGF-induced responses. By contrast, the membrane-anchored metalloproteinases, membrane-type 1 MMP, membrane-type 2 MMP, and membrane-type 3 MMP (MT1-, MT2-, and MT3-MMP) each modified the morphogenic program. Of the three MT-MMPs tested, only MT1-MMP and MT2-MMP were able to directly confer invasion-incompetent cells with the ability to penetrate type I collagen matrices. MT-MMP–dependent invasion proceeded independently of proMMP-2 activation, but required the enzymes to be membrane-anchored to the cell surface. These findings demonstrate that MT-MMP–expressing cells can penetrate and remodel type I collagen-rich tissues by using membrane-anchored metalloproteinases as pericellular collagenases.
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影响因子：
64.5
作者：
Hiraoka, N;Allen, E;Weiss, SJ
通讯作者：
Weiss, SJ
影响因子：
15.9
作者：
Dunsmore, SE;Saarialho-Kere, UK;Parks, WC
通讯作者：
Parks, WC
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
7.8
作者：
Lochter, A;Galosy, S;Muschler, J;Freedman, N;Werb, Z;Bissell, MJ
通讯作者：
Bissell, MJ
影响因子：
4.8
作者：
AIMES, RT;QUIGLEY, JP
通讯作者：
QUIGLEY, JP